期刊
CELL DEATH AND DIFFERENTIATION
卷 17, 期 10, 页码 1636-1644出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cdd.2010.40
关键词
cAMP pathway; neurodegeneration; excitotoxicity; apoptosis; inflammation
资金
- European Commission [LSHM-CT-2005-19063]
- Spanish Ministry of Science and Innovation [BFU2005-00286, CSD2007-00023, SAF2008-00611, BFU2006-01896]
- Generalitat Valenciana [GVPRE/2008/365]
- Fundacio La Marato de TV3 [063510]
- Junta de Comunidades de Castilla-La Mancha [PAI08-0174-6967]
We compare here the neurodegenerative processes observed in the hippocampus of bitransgenic mice with chronically altered levels of cAMP-response element-binding protein (CREB) function. The combination of genome-wide transcriptional profiling of degenerating hippocampal tissue with microscopy analyses reveals that the sustained inhibition of CREB function in A-CREB mice is associated with dark neuron degeneration, whereas its strong chronic activation in VP16-CREB mice primarily causes excitotoxic cell death and inflammation. Furthermore, the meta-analysis with gene expression profiles available in public databases identifies relevant common markers to other neurodegenerative processes and highlights the importance of the immune response in neurodegeneration. Overall, these analyses define the ultrastructural and transcriptional signatures associated with these two forms of hippocampal neurodegeneration, confirm the importance of fine-tuned regulation of CREB-dependent gene expression for CA1 neuron survival and function, and provide novel insight into the function of CREB in the etiology of neurodegenerative processes. Cell Death and Differentiation (2010) 17, 1636-1644; doi:10.1038/cdd.2010.40; published online 16 April 2010
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